Proton versus Intensity-Modulated Radiotherapy for Prostate Cancer

Patterns of Care and Early Toxicity

James B. Yu; Pamela R. Soulos; Jeph Herrin; Laura D. Cramer; Arnold L. Potosky; Kenneth B. Roberts; Cary P. Gross


J Natl Cancer Inst. 2013;105(1):25-32. 

In This Article

Abstract and Introduction


Background Proton radiotherapy (PRT) is an emerging treatment for prostate cancer despite limited knowledge of clinical benefit or potential harms compared with other types of radiotherapy. We therefore compared patterns of PRT use, cost, and early toxicity among Medicare beneficiaries with prostate cancer with those of intensity-modulated radiotherapy (IMRT).

Methods We performed a retrospective study of all Medicare beneficiaries aged greater than or equal to 66 years who received PRT or IMRT for prostate cancer during 2008 and/or 2009. We used multivariable logistic regression to identify factors associated with receipt of PRT. To assess toxicity, each PRT patient was matched with two IMRT patients with similar clinical and sociodemographic characteristics. The main outcome measures were receipt of PRT or IMRT, Medicare reimbursement for each treatment, and early genitourinary, gastrointestinal, and other toxicity. All statistical tests were two-sided.

Results We identified 27,647 men; 553 (2%) received PRT and 27,094 (98%) received IMRT. Patients receiving PRT were younger, healthier, and from more affluent areas than patients receiving IMRT. Median Medicare reimbursement was $32,428 for PRT and $18,575 for IMRT. Although PRT was associated with a statistically significant reduction in genitourinary toxicity at 6 months compared with IMRT (5.9% vs 9.5%; odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38 to 0.96, P = .03), at 12 months post-treatment there was no difference in genitourinary toxicity (18.8% vs 17.5%; OR = 1.08, 95% CI = 0.76 to 1.54, P = .66). There was no statistically significant difference in gastrointestinal or other toxicity at 6 months or 12 months post-treatment.

Conclusions Although PRT is substantially more costly than IMRT, there was no difference in toxicity in a comprehensive cohort of Medicare beneficiaries with prostate cancer at 12 months post-treatment.


Over the past decade, intensity modulated radiotherapy (IMRT) has become the standard form of radiotherapy for the treatment of prostate cancer, accounting for more than 80% of all radiotherapy.[1] Even as IMRT has been widely adopted, other radiotherapy modalities have come to market, most notably proton radiotherapy (PRT). Although PRT predates IMRT, dissemination of PRT has been increasing rapidly in recent years. In part because of its high capital cost, Medicare is reported to reimburse PRT at a rate 1.4 to 2.5 times that of IMRT,[2–4] despite many unexplored questions.

First, there is a lack of data regarding national patterns of use and the true cost of PRT among Medicare beneficiaries. Currently, there are only nine PRT centers in operation in the United States,[5] and this relatively low treatment capacity limits costs. However, eight other centers are in development,[5] along with smaller and more affordable proton machines,[6] conceivably opening the door to more widespread adoption of PRT across the country.

Second, the Institute for Clinical and Economic Review concluded unanimously that the state of current knowledge of comparative clinical effectiveness was "insufficient".[7,8] Because differences in cancer cure rates and survival from prostate cancer treatment often take many years to become evident, it has been suggested that initial study of prostate cancer treatments should focus on treatment-related toxicity.[8] Proponents of PRT argue that the physical properties of protons may decrease the most common side effects associated with prostate radiotherapy—gastrointestinal and genitourinary toxicity.[9] Early outcomes from single-arm, prospective trials investigating PRT are forthcoming, indicating low levels of radiation-induced toxicity with early follow-up.[10,11] However, IMRT itself has a robust literature describing excellent efficacy and low toxicity in the treatment of prostate cancer.[12] Therefore, it is unclear that PRT offers a statistically significant benefit beyond IMRT. Prior studies investigating PRT in Medicare beneficiaries using the Surveillance, Epidemiology, and End Results–Medicare database have been single-institution studies[13,14] and, therefore, are not of the whole country. These studies[13,14] noted a statistically significant reduction of gastrointestinal toxicity for patients undergoing IMRT compared with PRT. A comprehensive comparison of PRT with IMRT requires examination of the entire country for the most recent years available.

As more PRT centers become operational, it will be crucial for patients, providers, and policy makers to understand the cost and national pattern of adoption of PRT and the incidence of treatment-related toxicity compared with IMRT. Therefore, we used a national sample of Medicare beneficiaries with prostate cancer to investigate the patterns and cost of PRT delivery, as well as the early treatment-related toxicity associated with PRT compared with IMRT.